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Nitrosative stress induces osteoblast apoptosis through downregulating MAPK-mediated NFkappaB/AP-1 activation and

Ta-Liang Chen1, Gong-Jhe Wu, Chun-Sen Hsu

  • 1Department of Anesthesiology, Taipei Medical University, Taipei, Taiwan.

Chemico-Biological Interactions
|February 6, 2010
PubMed

Insights

Sodium nitroprusside (SNP) causes nitrosative stress, increasing reactive oxygen species and damaging rat osteoblasts. This damage involves decreased Bcl-X(L) expression and impaired MAPK/NF-κB/AP-1 signaling, leading to apoptosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Toxicology

Background:

  • Inflammation generates reactive oxygen species (ROS), which can damage osteoblasts.
  • Understanding the molecular mechanisms of such damage is crucial for bone health.

Purpose of the Study:

  • To investigate the molecular mechanisms by which sodium nitroprusside (SNP) induces damage to rat osteoblasts.
  • To elucidate the role of nitrosative stress, apoptosis, and specific signaling pathways in SNP-induced osteoblast insult.

Main Methods:

  • Osteoblasts from neonatal rat calvaria were exposed to SNP.
  • Measurements included nitric oxide, ROS, Bcl-X(L) mRNA and protein, transcription factor translocation (NF-κB, AP-1), and MAPK phosphorylation.
  • Small interfering RNAs (siRNAs) for ERK1 and JNK1 were used to assess their role.

Main Results:

  • SNP exposure increased nitric oxide and ROS, inducing apoptosis in a dose- and time-dependent manner.
  • SNP decreased antiapoptotic Bcl-X(L) expression and inhibited NF-κB and AP-1 activation.
  • SNP reduced the phosphorylation of ERK1/2, JNK1/2, and p38 MAPK.
  • siRNA-mediated knockdown of ERK1/2 and JNK1 exacerbated SNP-induced apoptosis and Bcl-X(L) downregulation.

Conclusions:

  • SNP-induced nitrosative stress leads to osteoblast apoptosis.
  • This process involves the downregulation of Bcl-X(L) expression.
  • The mechanism includes the suppression of MAPK phosphorylation, subsequently affecting NF-κB and AP-1 activation.

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